Orally Deliverable Microalgal-Based Carrier with Selenium Nanozymes for Alleviation of Inflammatory Bowel Disease.

Excessive reactive oxygen species (ROS) is a hallmark of both the onset and progression of inflammatory bowel disease (IBD), where a continuous cycle of ROS and inflammation drives the progression of diseases. The design of oral antioxidant nanoenzymes for scavenging ROS has emerged as a promising strategy to intervene in IBD. However, the practical application of these nanoenzymes is limited due to their single catalytical property and significantly impacted by substantial leakage in the upper gastrointestinal tract. This study introduces a novel oral delivery system, SP@CS-SeNPs, combining natural microalgae Spirulina platensis (SP), which possesses superoxide dismutase (SOD)-like activity, with chitosan-functionalized selenium nanoparticles (CS-SeNPs) that exhibit catalase-like activity. The SP@CS-SeNPs system leverages the dual catalytic capabilities of these components to initiate a cascade reaction that first converts superoxide anion radicals (O2•-) into hydrogen peroxide (H2O2), and then catalyzes the decomposition of H2O2 into water and oxygen. This system not only utilizes the resistance of the microalgae carrier to gastric acid and its efficient capture by intestinal villi, thereby enhancing intestinal distribution and retention but also demonstrates significant anti-inflammatory effects and effective repair of the damaged intestinal barrier in a colitis mice model. These results demonstrate that this oral delivery system successfully combines the features of microalgae and nanozymes, exhibits excellent biocompatibility, and offers a novel approach for antioxidant nanozyme intervention in IBD.

Dual-layer probiotic encapsulation using metal phenolic network with gellan gum-tamarind gum coating for colitis treatment.

Probiotic oral therapy has been recognised as an effective treatment for inflammatory bowel disease (IBD). However, the efficacy of probiotics is often diminished due to their limited resistance to harsh gastrointestinal conditions. Therefore, the importance of designing innovative strategies for oral probiotic delivery for the effective treatment of IBD is increasingly recognised. In this study, we present a novel encapsulation strategy of Lactobacillus plantarum (L.P) using the dual-layer system consisting of a tannic acid­calcium network and polysaccharide coating (gellan gum-tamarind gum) named L.P-C/T-G/T. This double-layer encapsulation system not only does not affect the normal proliferation of probiotics and provide protection, but also endows probiotics with more functions. More specifically, the acid resistance ability of the encapsulated probiotics is increased by 10 times, the free radical scavenging rate is enhanced by 5 times, and the intestinal retention time can be prolonged by 6-12 h. In the DSS-induced murine colitis model, it significantly alleviated colon shortening, inhibited ROS overexpression, and promoted the repair and regeneration of the mucus layer. This dual-layer encapsulation approach for a single probiotic demonstrates a significant advancement in probiotic delivery technology, offering hope for a comprehensive approach to the treatment of colitis and potentially other gastrointestinal disorders.

Physical properties and antioxidant activity of curcumin­zinc metal-organic frameworks.

Metal-organic frameworks (MOFs) offer diverse applications in the food industry, facilitating loading, protection, and controlled release of functional ingredients despite encountering loading capacity and functional activity limitations. This study focuses on curcumin­zinc MOFs, harnessing curcumin's renowned health benefits and zinc to enhance pharmacological properties. We evaluated their synthesis efficiency, stability under varying conditions (pH, salt concentration, temperature), loading and antioxidant capacity. The results showed that microwave synthesis yielded MOFs with a 23.2 ± 4.5% yield, stable within pH 4-10, gradually decomposing in PBS. DPPH, ABTS, and H2O2 assays revealed varying free radical scavenging abilities. MOFs disintegrate in either acidic environments or contain H2O2 (at a concentration threshold of 10 µM). Post-disintegration, these MOFs significantly inhibiting the secretion of TNF-α by RAW264.7 cells induced by LPS. These findings highlight the potential of novel curcumin­zinc MOF materials for nutrient delivery, addressing challenges in effectively delivering functional ingredients.

Morin-Based Nanoparticles for Regulation of Blood Glucose.

Morin, a naturally occurring bioactive compound shows great potential as an antioxidant, anti-inflammatory agent, and regulator of blood glucose levels. However, its low water solubility, poor lipid solubility, limited bioavailability, and rapid clearance in vivo hinder its application in blood glucose regulation. To address these limitations, we report an enzymatically synthesized nanosized morin particle (MNs) encapsulated in sodium alginate microgels (M@SA). This approach significantly enhances morin's delivery efficiency and therapeutic efficacy in blood glucose regulation. Utilizing horseradish peroxidase, we synthesized MNs averaging 305.7 ± 88.7 nm in size. These MNs were then encapsulated via electrohydrodynamic microdroplet spraying to form M@SA microgels. In vivo studies revealed that M@SA microgels demonstrated prolonged intestinal retention and superior efficacy compared with unmodified morin and MNs alone. Moreover, MNs notably improved glucose uptake in HepG2 cells. Furthermore, M@SA microgels effectively regulated blood glucose, lipid profiles, and oxidative stress in diabetic mice while mitigating liver, kidney, and pancreatic damage and enhancing anti-inflammatory responses. Our findings propose a promising strategy for the oral administration of natural compounds for blood glucose regulation, with implications for broader therapeutic applications.

Construction of diallyltrisulfide nanoparticles for alleviation of ethanol-induced acute gastric injury.

Gastric ulcer, a significant health issue characterized by the degradation of the gastric mucosa, often arises from excessive gastric acid secretion and poses a challenge in current medical treatments due to the limited efficacy and side effects of first-line drugs. Addressing this, our study develops a novel therapeutic strategy leveraging gas therapy, specifically targeting the release of hydrogen sulfide (H2S) in the treatment of gastric ulcers. We successfully developed a composite nanoparticle, named BSA·SH-DATS, through a two-step process. Initially, bovine serum albumin (BSA) was sulfhydrated to generate BSA·SH nanoparticles via a mercaptosylation method. Subsequently, these nanoparticles were further functionalized by incorporating diallyltrisulfide (DATS) through a precise Michael addition reaction. This sequential modification resulted in the creation of BSA·SH-DATS nanoparticles. Our comprehensive in vitro and in vivo investigations demonstrate that these nanoparticles possess an exceptional ability for site-specific action on gastric mucosal cells under the controlled release of H2S in response to endogenous glutathione (GSH), markedly diminishing the production of pro-inflammatory cytokines, thereby alleviating inflammation and apoptosis. Moreover, the BSA·SH-DATS nanoparticles effectively regulate critical inflammatory proteins, including NF-κB and Caspase-3. Our study underscores their potential as a transformative approach for gastric ulcer treatment.

Construction of Magnolol Nanoparticles for Alleviation of Ethanol-Induced Acute Gastric Injury.

Ethanol (EtOH) has been identified as a potential pathogenic factor in gastric ulcer development primarily due to its association with gastric injury and excessive production of reactive oxygen species. Magnolol (Mag), the principal active compound in Magnolia officinalis extract, is well studied for its notable anti-inflammatory and antioxidant properties. However, its limited solubility, propensity for agglomeration, and low absorption and utilization rates significantly restrict its therapeutic use. This study aims to overcome these challenges by developing a Mag nanoparticle system targeting the treatment and prevention of EtOH-induced gastric ulcers in mice. Utilizing a click chemistry approach, we successfully synthesized this system by reacting thiolated bovine serum albumin (BSA·SH) with Mag. The in vitro analysis revealed effective uptake of the BSA·SH-Mag nanoparticle system by human gastric epithelial cells (GES-1), showcasing its antioxidant and anti-inflammatory capabilities. Additionally, BSA·SH-Mag exhibited gradual disintegration and release in simulated gastric fluid, resulting in a notable reduction of oxidative stress in gastric tissues and mucosal tissue repair and effectively reducing inflammatory expression. Furthermore, BSA·SH-Mag attenuated EtOH-induced gastric inflammation by decreasing the level of NOX4 protein expression and augmenting the level of Nrf2 protein expression. In conclusion, our findings indicate that BSA·SH-Mag represents a promising candidate as an oral therapeutic for gastric ulcer treatment.

Angelica sinensis polysaccharides modified selenium nanoparticles for effective prevention of acute liver injury.

As a global public health issue, the treatment of acute liver injury (ALI) is severely limited due to the lack of specific drugs. In order to address the challenges, innovative strategies for selenium nanoparticles (Se NPs) with excellent antioxidant properties have been actively developed to effectively prevent ALI. However, the functional activity of Se NPs is severely affected by poor stability and bioavailability. The aim of this work is to develop a stabilization system (ASP-Se NPs) for Angelica sinensis polysaccharides modified Se NPs. The results showed that ASP-Se NPs with smaller size (62.38 ± 2.96 nm) showed good stability, specific accumulation in liver and enhanced cell uptake, thus exerting strong antioxidant and anti-inflammatory functions. The results of in vivo experiments further confirmed that ASP-Se NPs effectively prevented CCl4-induced ALI by improving liver function, inhibiting oxidative stress and inflammatory response, and liver pathological damage. This work provides a new alternative method for effectively preventing ALI and improving liver function.

Development of nano-delivery systems for loaded bioactive compounds: using molecular dynamics simulations.

Over the past decade, a remarkable surge in the development of functional nano-delivery systems loaded with bioactive compounds for healthcare has been witnessed. Notably, the demanding requirements of high solubility, prolonged circulation, high tissue penetration capability, and strong targeting ability of nanocarriers have posed interdisciplinary research challenges to the community. While extensive experimental studies have been conducted to understand the construction of nano-delivery systems and their metabolic behavior in vivo, less is known about these molecular mechanisms and kinetic pathways during their metabolic process in vivo, and lacking effective means for high-throughput screening. Molecular dynamics (MD) simulation techniques provide a reliable tool for investigating the design of nano-delivery carriers encapsulating these functional ingredients, elucidating the synthesis, translocation, and delivery of nanocarriers. This review introduces the basic MD principles, discusses how to apply MD simulation to design nanocarriers, evaluates the ability of nanocarriers to adhere to or cross gastrointestinal mucosa, and regulates plasma proteins in vivo. Moreover, we presented the critical role of MD simulation in developing delivery systems for precise nutrition and prospects for the future. This review aims to provide insights into the implications of MD simulation techniques for designing and optimizing nano-delivery systems in the healthcare food industry.

Metal-polyphenol microgels for oral delivery of puerarin to alleviate the onset of diabetes.

Puerarin (Pue) is a naturally bioactive compound with many potential functions in regulating blood glucose and lipid metabolism. However, the low bioavailability and rapid elimination in vivo limit the application of Pue in diabetic treatment. Here, we developed a metal-polyphenol-functionalized microgel to effectively deliver Pue in vivo and eventually alleviate the onset of diabetes. Pue was initially encapsulated in alginate beads through electrospray technology, and further immersed in Fe3+ and tannic acid solution from tannic acid (TA)-iron (Fe) coatings (TF). These constructed Pue@SA-TF microgels exhibited uniform spheres with an average size of 367.89 ± 18.74 µm and high encapsulation efficiency of Pue with 61.16 ± 1.39%. In vivo experiments proved that compared with free Pue and microgels without TF coatings, the biological distribution of Pue@SA-TF microgels specifically accumulated in the small intestine, prolonged the retention time of Pue, and achieved a high effectiveness in vivo. Anti-diabetic experimental results showed that Pue@SA-TF microgels significantly improved the levels of blood glucose, blood lipid, and oxidative stress in diabetic mice. Meanwhile, histopathological observations indicated that Pue@SA-TF microgels could significantly alleviate the damage to the liver, kidney, and pancreas in diabetic mice. Our study provided an effective strategy for oral delivery of Pue and achieved high anti-diabetic efficacy.

Porphyra haitanensis polysaccharide-functionalized selenium nanoparticles for effective alleviation of ulcerative colitis.

Exacerbated intestinal inflammation, oxidative stress imbalance, and damage to intestinal mucosal barrier are closely related to the pathogenesis and progression of ulcerative colitis (UC). Selenium nanoparticles (Se NPs) have demonstrated promising potential to alleviate UC symptoms, however, their poor solubility and stability leading to aggregation and large precipitates have significantly limit their clinical application. In this study, we aimed to enhance the performance of Se NPs by functionalizing them with Porphyra haitanensis polysaccharide, yielding PHP-Se NPs. As expected, these PHP-Se NPs exhibited reduced particle size (70.51 ± 2.92 nm), enhanced cellular uptake compared to native Se NPs, and preferential accumulation in the colonic tissue, providing targeted UC treatment. In vivo animal experiments revealed that PHP-Se NPs significantly improved weight loss, shortened colon length, and higher disease activity index (DAI) scores in DSS-induced UC mice. Moreover, PHP-Se NPs significantly inhibited the levels of inflammatory factors in colitis tissues and oxidative stress in serum of UC mice, improved histological damage in colitis tissues, and restored the intestinal mucosal barrier. Taken together, our study offers an innovative approach to augment the bioavailability of Se NPs, presenting a promising strategy for the effective prevention and management of UC.

Cyclodextrin-based metal-organic framework materials: Classifications, synthesis strategies and applications in variegated delivery systems.

Metal-organic frameworks (MOFs) are coordination compounds that possess an adjustable structure and controllable function. Despite their wide applications in various industries, the use of MOFs in the fields of food and biomedicine is limited mainly due to their potential biological toxicity. Researchers have thus focused on developing biocompatible MOFs to address this issue. Among them, cyclodextrin-based metal-organic frameworks (CD-MOFs) have emerged as a promising alternative. CD-MOFs are novel MOFs synthesized using naturally carbohydrate cyclodextrin and alkali metal cations, and possess renewable, non-toxic, and edible characteristics. Due to their high specific surface area, controllable porosity, great biocompatibility, CD-MOFs have been widely used in various delivery systems, such as encapsulation of nutraceuticals, flavors, and antibacterial agents. Although the field of CD-MOF materials is still in its early stages, they provide a promising direction for the development of MOF materials in the delivery field. This review describes classification and structural characteristics, followed by an introduction to formation mechanism and commonly used synthetic methods for CD-MOFs. Additionally, we discuss the status of the application of various delivery systems based on CD-MOFs. Finally, we address the challenges and prospects of CD-MOF materials, with the aim of providing new insights and ideas for their future development.

Tendon-inspired hybrid hydrogel based on polyvinyl alcohol and gallic acid-lysozyme for promoting wound closure and healing.

Noninvasive wound closure remains a challenge in the field of wound healing. In this study, we report the development of a cross-linked P-GL hydrogel constructed from polyvinyl alcohol (PVA) and GL (a hydrogel consisting of gallic acid and lysozyme) that effectively promotes wound closure and healing. The P-GL hydrogel exhibited a unique lamellar and tendon-like fibrous network structure, providing good thermo-sensitivity and tissue adhesiveness up to 60 MPa, as well as retaining autonomous self-healing and acid resistance capacities. In addition, the P-GL hydrogel exhibited sustained release characteristics lasting >100 h, excellent biocompatibility both in vitro and in vivo, as well as good antibacterial activity and mechanical properties. The in vivo full-thickness skin wounds model revealed the positive wound closure and healing therapeutic effects of the P-GL hydrogels were confirmed, showing a promising potential as a noninvasive wound closure and healing bio-adhesive hydrogel.

Colon-Targeting Angelica sinensis Polysaccharide Nanoparticles with Dual Responsiveness for Alleviation of Ulcerative Colitis.

Intestinal immune dysfunction and gut microbiota dysbiosis are critically causative factors in the pathogenesis of ulcerative colitis (UC); however, the current first-line drugs for UC treatment in clinics often remain great challenges due to their nontargeting therapeutic efficacy and severe side effects. In the current study, colon-targeting nanoparticles based on Angelica sinensis polysaccharide with pH- and redox-responsiveness were fabricated to specifically release the naturally active compound ginsenoside Rh2 in the colonic inflammatory site, which greatly alleviated the UC symptoms and improved the gut microbial homeostasis. These dual responsive Rh2-loaded nanoparticles (Rh2/LA-UASP NPs) with a particle size of 117.00 ± 4.80 nm were prepared using the polymer LA-UASP obtained by grafting A. sinensis polysaccharide with urocanic acid and α-lipoic acid (α-LA). As expected, these Rh2/LA-UASP NPs achieved dual pH- and redox-responsive drug release at pH 5.5 and 10 mM GSH. The stability, biocompatibility, and in vivo safety experiments exhibited these prepared nanoparticles had excellent colon-targeting ability and significant accumulation of Rh2 in the inflammatory colon. Meanwhile, these Rh2/LA-UASP NPs could escape from lysosomes and be efficiently internalized into intestinal mucosal cells, thereby effectively inhibiting the release of proinflammatory cytokines. The animal experiments indicated that Rh2/LA-UASP NPs significantly improved the integrity of intestinal mucosa and increased the colon length compared with UC mice. Additionally, the weight loss, histological damage, and inflammation level were greatly ameliorated. The homeostasis of intestinal flora and the level of short-chain fatty acids (SCFAs) were significantly improved after being treated with Rh2/LA-UASP NPs in UC mice. Our study proved that these Rh2/LA-UASP NPs with dual pH-and redox-responsiveness are promising candidates for UC treatment.

Mucoadhesive Hydrogel with Anti-gastric Acid and Sustained-Release Functions for Amelioration of DSS-Induced Ulcerative Colitis.

Mucoadhesive hydrogels with multifunctional properties such as gastric acid resistance and sustained drug release in the intestinal tract are highly desirable for the oral treatment of inflammatory bowel diseases (IBDs). Polyphenols are proven to have great efficacies compared with the first-line drugs for IBD treatments. We recently reported that gallic acid (GA) was capable of forming a hydrogel. However, this hydrogel is prone to easy degradation and poor adhesion in vivo. To tackle this problem, the current study introduced sodium alginate (SA) to form a gallic acid/sodium alginate hybrid hydrogel (GAS). As expected, the GAS hydrogel showed excellent antiacid, mucoadhesive, and sustained degradation properties in the intestinal tract. In vitro studies demonstrated that the GAS hydrogel significantly alleviated ulcerative colitis (UC) in mice. The colonic length of the GAS group (7.75 ± 0.38 cm) was significantly longer than that of the UC group (6.12 ± 0.25 cm). The disease activity index (DAI) value of the UC group was (5.5 ± 0.57), which was markedly higher than that of the GAS group (2.5 ± 0.65). The GAS hydrogel also could inhibit the expression of inflammatory cytokines, regulating macrophage polarization and improving the intestinal mucosal barrier functions. All these results indicated that the GAS hydrogel was an ideal candidate for oral treatment of UC.

Construction of an antibacterial hydrogel based on diammonium glycyrrhizinate and gallic acid for bacterial- infected wound healing.

The current antibacterial wound dressings with antibiotic substances or metal bactericidal agents may lead to severe multidrug resistance and poor biocompatibilities. Herein, we report an inherent antibacterial hydrogel constructed by only two naturally small molecules gallic acid (GA) and diammonium glycyrrhizinate (DG) for promoting Staphylococcus aureus (S. aureus)-infected wound healing. The resultant GAD hydrogel can be fabricated by co-assembly of these two materials through simple steps. Thanks to the incorporation of GA and DG, GAD hydrogel enabled a strong mechanical performance and great self-healing property with a sustained-release of drugs into skin wounds. Moreover, the cell viability assays showed that GAD hydrogel had good cytocompatibility by promoting cell proliferation and migration. In addition, GAD hydrogel had broad antibacterial efficiency against both Gram-positive and Gram-negative bacteria. Taken together, GAD hydrogel is a promising dressing to accelerate bacterial-infected wound healing through reconstructing an intact and thick epidermis without antibiotics or cytokines.

Coassembly of Fiber Hydrogel with Antibacterial Activity for Wound Healing.

Wound healing remains a critical challenge due to its vulnerability to bacterial infection and the complicated inflammatory microenvironment. Herein, we report a novel antibacterial hydrogel constructed only by gallic acid (GA) and phycocyanin (PC), which is expected for the treatment of bacteria-infected wounds. These GA/PC hydrogels (GP) was found to coassemble into fibrous networks with a diameter of around 2 µm mainly through noncovalent interactions of hydrogen bonds, van der Waals force, and π interaction. Notably, these GP hydrogels showed excellent rheological properties (i.e., storage modulus of more than 9.0 × 104 Pa) and outstanding biocompatibility and antibacterial activities. Thanks to the incorporation of GA and PC, the GP hydrogels enabled adherence to the moist wound tissue and achieved a sustained release of GA and PC into the wound skin, therefore effectively attenuating inflammation and accelerating wound healing both in normal mice and bacteria-infected mice through regulating the expression of the tight junction protein and the alleviation of oxidative stress. Considering these results, these GP hydrogels are demonstrated to be a promising candidate for bacteria-infected wound healing.

Construction of a sustained-release hydrogel using gallic acid and lysozyme with antimicrobial properties for wound treatment.

The purpose of this study is to provide a new strategy for constructing a temperature-controlled hydrogel as a promising agent for wound healing using natural products through physical co-assembly. Herein, the temperature-controlled physically assembled hydrogel consisting of gallic acid and lysozyme (GL) could be co-assembled into a regular fibrous structure accompanied by strong blue fluorescence with three-dimensional networks at micron levels through hydrophobic interactions, π-π interactions and hydrogen bonding. This GL hydrogel has excellent temperature sensitivity and self-healing properties, as proved by cycle high-low temperature tests. In addition, it possesses stable rheological properties, great sustained release ability, and could realize the spatiotemporal delivery of gallic acid and lysozyme. Biocompatibility and antibacterial tests proved that this well-assembled GL hydrogel has no cytotoxicity but excellent antibacterial activity. Both in vitro and in vivo experiments demonstrated that the GL hydrogel has excellent anti-inflammation efficiency and promotes the healing of chronic wounds by suppressing the expression of pro-inflammatory related genes. Tests using an E. coli-infected wound model confirmed that the GL hydrogel could terminate the inflammatory phase early and ultimately promote the healing of wounds infected by E. coli. This study provides a promising strategy for the effective treatment of wounds through a physical self-assembled hydrogel.

Construction of novel magnetic nanoparticles for enrichment of benzo(α)pyrene from edible oils followed by HPLC determination.

A novel method for benzo(α)pyrene (Bαp) enrichment from an oil matrix was developed by using magnetic nanoparticles (Fe3O4@dopamine/graphene oxide, Fe3O4@DA/GO) as extraction absorbents, and the chemical properties of the synthesized nanoparticles were characterized. Various parameters were investigated to optimize the extraction of Bαp from oils. Under optimal conditions (pH, 4; extraction time, 0.5 min; elution solvent, 1 mL; absorbent weight, 20 mg; elution time, 0.5 min), these nanoparticles showed excellent abilities to enrich Bαp from the saponified oil solution and were easily separated by a magnet. High-performance liquid chromatography plus fluorescence detection (HPLC-FLD) was then applied to determine the Bαp content with excellent linearity (R2 = 0.999). The detection limit was 0.13 µg/kg, while the limit of quantification was 0.42 µg/kg. The spiked recoveries of Bαp in oils ranged from 73.5% to 121%. Compared with previous reports, the proposed method displayed many advantages, including a high efficiency of oil matrix removal, short extraction time, and convenient extraction procedure.

Resveratrol Triggered the Quick Self-Assembly of Gallic Acid into Therapeutic Hydrogels for Healing of Bacterially Infected Wounds.

Programing self-assembly of naturally bioactive molecules has been a wide topic of great significance for biomedical uses. Despite the fact that plant-derived polyphenols with catechol or pyrogallol moieties have been widely studied to construct nanocomplexes or nanocoatings via self-polymerization, there is no report on the self-assembly of these polyphenols into therapeutic hydrogels for potential applications. Here, we reported that adding a very small amount of resveratrol (Res) into the gallic acid (GA) aqueous solution could trigger the quick self-assembly of GA to form a fibrous hydrogel within 5 min through hydrogen bonds and π-π interactions. The length of GA/Res (GR) fibrils in gels varied from 100 to 1000 microns, with a diameter of around 1 µm. Notably, these GR hydrogels showed excellent colloid stability, providing better slow release and outstanding biocompatibility. Also, in vivo experiments indicated the hydrogels had high antibacterial effects and excellent wound healing capabilities in a total skin defect model via regulating the expression of inflammatory factors (IL-6, IL-1ß, and TNF-α) due to the release of therapeutic agents (GA and Res) into the matrix. Overall, our results provide a new strategy to accelerate self-assembly of GA by adding Res to form hydrogels, which is further proved as a promising therapeutic carrier for wound healing.